7. PROJECT SUMMARY / ABSTRACT A developing yet still inconclusive literature suggests that exposures early in life may play an important role in health disparities found at older ages. This literature suggests that early life environment may be a key place for intervening to reduce health disparities in the most cost-effective manner. A separate literature has suggested that environmental factors early in life have an important impact on patterns of DNA methylation that extend into old age. However, there remains a critical gap in knowledge of how DNA methylation may be a key underlying mechanism of linking early life exposures to racial/ethnic and socioeconomic disparities in chronic disease. This application seeks funding for innovative exploratory work to test whether linking current longitudinal cohorts to historical individual level data from the 1940 U.S. Census at the time of childhood will offer a solution to answering this critical question. Our long-term goal is to understand the extent to which DNA methylation contributes to racial/ethnic and socioeconomic disparities in chronic disease incidence. The overall objective of this application is to test whether linkage to administrative data from the U.S. Census is an efficient and effective way of determining links between the early life environment and disparities in health due to changes in DNA methylation. Our central hypothesis, based on the literature and our prior research, is that early life household conditions will have a substantial impact on both racial/ethnic and socioeconomic disparities in DNA methylation. To test this hypothesis we propose the following three specific aims: Aim 1: Link Women's Health Initiative study participants to their childhood household data from the 1940 U.S. full population census, Aim 2: Test the association between early life household environment and racial/ethnic and socioeconomic differences in DNA methylation later in life, Aim 3: Perform quantitative bias analysis to assess the likelihood of bias due to differential linkage, survival, and study participation by race/ethnicity and socioeconomic position. The innovation of our proposed research is in testing a new approach to capturing the early life environment that does not rely on retrospective self-reports. If validated, our approach could be applied to dozens of other currently available cohort studies with DNA methylation data that have participants who were alive in 1940. Critically, the 1940 U.S. census measures could then become a commonly used environmental metric applied across multiple studies facilitating large-scale meta-analyses of environmental impacts on health. Overall, we believe our innovative, exploratory study has the potential to guide a large number of future studies that will allow robust and useful estimates of how the early life environment contributes to differences in DNA methylation and subsequent chronic disease disparities. We believe our approach represents a very cost-effective and efficient means to leverage currently available DNA methylation data to study the impact of the early life environment on health disparities.